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Elife 2022 Aug 09;11. doi: 10.7554/eLife.73818.
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Positive feedback regulation of frizzled-7 expression robustly shapes a steep Wnt gradient in Xenopus heart development, together with sFRP1 and heparan sulfate.

Yamamoto T , Kambayashi Y , Otsuka Y , Afouda BA , Giuraniuc C , Michiue T , Hoppler S .

Secreted molecules called morphogens govern tissue patterning in a concentration-dependent manner. However, it is still unclear how reproducible patterning can be achieved with diffusing molecules, especially when that patterning concerns differentiation of thin tissues. Wnt is a morphogen that organizes cardiac development. Wnt6 patterns cardiogenic mesoderm to induce differentiation of a thin tissue, the pericardium, in Xenopus. In this study, we revealed that a Wnt receptor, frizzled-7, is expressed in a Wnt-dependent manner. With a combination of experiments and mathematical modeling, this receptor-feedback appears essential to shape a steep gradient of Wnt signaling. In addition, computer simulation revealed that this feedback imparts robustness against variations of Wnt ligand production and allows the system to reach a steady state quickly. We also found that a Wnt antagonist sFRP1, which is expressed on the opposite side of the Wnt source, accumulates on N-acetyl-rich heparan sulfate (HS). N-acetyl-rich HS concentration is high between the sources of Wnt and sFRP1, achieving local inhibition of Wnt signaling via restriction of sFRP1 spreading. These integrated regulatory systems restrict the Wnt signaling range and ensure reproducible patterning of the thin pericardium.

PubMed ID: 35942683
Article link: Elife
Grant support: [+]

Species referenced: Xenopus laevis
Genes referenced: fzd7 gata5 myl2 ndst1 odc1 sfrp1 tnni3 wnt6
GO keywords: heart development
Morpholinos: wnt6 MO1

Article Images: [+] show captions
References [+] :
Abu-Elmagd, Frizzled7 mediates canonical Wnt signaling in neural crest induction. 2006, Pubmed, Xenbase